Normal serum can increase the rate of lipolysis in isolated adipocytes.
Recently, we reported that the lipolytic effect of serum could be
partly explained by effects of iron and transferrin. To further
investigate these effects on fat cell metabolism, we have investigated
effects of serum, iron, and transferrin on glucose transport in
isolated rat adipocytes. Adipocytes were isolated by collagenase
digestion of rat epididymal fat pads, and glucose transport was
measured as uptake of [(3)H]2-deoxyglucose, measured in the presence of
0 to 25 ng/mL insulin. Insulin stimulated glucose transport
approximately 8- to 10-fold, with a half-maximally effective
concentration (EC(50)) of approximately 0.15 ng/mL. This was not
affected by 45-minute treatment with normal human serum. However, when
adipocytes were incubated with serum for 4 hours, cells became markedly
insulin resistant. This was manifested as decrease in maximally
stimulated glucose transport and a rightward shift in the dose-response
curve. Both FeS0(4) (3 mug/mL) and transferrin (100 mug/mL) had
similar, although less pronounced effects on insulin-stimulated glucose
transport. Treatment of adipocytes with palmitic acid (120 mumol/L),
representing the concentration of fatty acids released into the media
after 4 hours of serum treatment, did not alter the effect of insulin
on glucose transport. We conclude that transferrin and iron induce
insulin resistance of glucose transport in adipocytes through a
mechanism independent of fatty acids. These findings may further
explain the association between body iron stores and risk of type 2
diabetes mellitus.